Our bodies are complex systems, but a surprising new study offers a fresh perspective on autism spectrum disorder (ASD), suggesting a profound link between a child’s gut health and their brain activity. Researchers at the University of Southern California (USC) indicate that imbalances in gut-produced chemicals may disrupt brain functions and contribute to behaviors associated with autism. This opens up promising possibilities for understanding and potentially addressing autism from an entirely new angle.
This research highlights the intricate “gut-brain axis,” a two-way communication highway between your digestive system and your brain. It reveals that the balance of tiny chemical compounds, called metabolites, created by the gut’s vast bacterial community, could play a significant role. If these findings hold up, a healthier gut might lead to a healthier brain, paving the way for innovative approaches to support individuals with ASD.
Unveiling the Gut-Brain Connection in ASD
To understand this connection, the USC team conducted a detailed study involving 43 children with ASD and 41 typically developing children, all between 8 and 17 years old. The participants provided stool samples, offering a snapshot of the chemical processes happening in their gut. Scientists specifically looked at metabolites linked to tryptophan, an amino acid found in many foods. Tryptophan is crucial because gut bacteria convert it into various compounds, some of which are known to influence brain activity. For instance, “much of the body’s serotonin originates in the gut microbiome, [and] changes in gut health can influence serotonin production” [Source: 13.txt].
The study also involved functional magnetic resonance imaging (fMRI) sessions. This advanced brain scanning technique measures changes in blood flow to different brain regions, revealing which parts of the brain are active during specific tasks. During the fMRI, children viewed images and videos designed to engage parts of the brain responsible for understanding emotions, facial expressions, and sensory experiences, tasks that often show differences in individuals with ASD.
Participants underwent comprehensive behavioral assessments as well, providing insights into their sensory sensitivities, social skills, and even sleep patterns. The researchers carefully selected participants, ensuring all had an IQ of at least 79 and were right-handed. They also excluded anyone who had recently taken antibiotics or probiotics, which could interfere with gut measurements. For the ASD group, diagnoses were confirmed using standard clinical assessments. By combining data from gut chemistry, brain scans, and observed behaviors, the researchers aimed to draw clearer connections between these seemingly separate areas.
Surprising Findings: Gut Chemicals Influence Brain Activity
A key finding was that children with ASD had significantly lower levels of a specific tryptophan-related metabolite called kynurenate in their stool samples compared to neurotypical children. This metabolite has been associated with protecting brain cells. Its reduced presence might indicate a lack of such protection during brain development.
These lower kynurenate levels, and other tryptophan-related metabolites, were directly linked to altered brain activity in the ASD group. Affected brain areas included the insular and cingulate cortices. The insula is involved in how we sense our internal body states, such as heart rate or discomfort, a process called interoception. The cingulate cortex plays a role in processing emotions, social interactions, and attention.
The study revealed direct associations between these gut metabolites, brain activity, and the severity of autism symptoms. For example, lower levels of a metabolite called indolelactate were connected to increased activity in the right mid-insula when children viewed images of disgusting foods. Given that individuals with ASD often process disgust differently, this is a notable observation. Furthermore, activity in the mid-insula and mid-cingulate brain regions acted as an intermediary, processing signals from these gut metabolites and influencing symptoms like overall autism severity and sensitivity to disgust. This suggests the brain plays a role in translating gut signals into observable behaviors.
Other interesting patterns emerged. For instance, higher levels of a metabolite called tryptophol correlated significantly with sensory sensitivities in children with ASD. Many individuals with ASD experience sensory differences, such as being overwhelmed by certain sounds. The study also noted that children with ASD generally had a higher body mass index (BMI), more gastrointestinal symptoms, and increased sensory sensitivities compared to the neurotypical group.
New Avenues for Understanding and Support
This study marks an important step toward understanding autism as a condition influenced by the body’s interconnected systems. It connects gut chemistry to specific brain functions and behaviors, bridging gaps in previous research. According to first author Lisa Aziz-Zadeh, “We demonstrated that gut metabolites impact the brain, and the brain, in turn, affects behavior. Essentially, the brain acts as the intermediary between gut health and autism-related behaviors.” She further added that while “previous studies highlighted differences in gut microbiomes and brain structures in autism, our research connects the dots” [Source: 13.txt].
The implications are significant. If gut imbalances indeed affect brain function and behavior in ASD, it opens new avenues for potential treatments. Future interventions might focus on modifying the gut environment through dietary changes or specific supplements to influence brain activity and alleviate symptoms, rather than solely relying on behavioral therapies or brain-targeted medications. Sofronia Ringold, a doctoral student who worked on the study, expressed excitement “by the possibility of interventions that might target the gut and influence neural activity and behavior while also hopefully alleviating some of the symptoms that are the most uncomfortable for them” [Source: 13.txt].
It is important to remember that this study observed correlations and mediating effects, rather than direct cause-and-effect relationships. To establish causality, future research would need to follow individuals over time or conduct studies where specific gut-focused treatments are introduced and their effects on the brain and behavior are directly measured. Despite this, the research provides compelling evidence for the dynamic interplay between the gut, brain, and behavior in autism, suggesting that supporting gut health could be a vital component in comprehensive care for individuals with ASD.
Paper Summary
Methodology
This cross-sectional, case-control observational study included 43 children with autism spectrum disorder (ASD) and 41 neurotypical children, aged 8 to 17. Researchers conducted fecal metabolomics, functional magnetic resonance imaging (fMRI) during socio-emotional and sensory tasks, and behavioral assessments. Participants were carefully selected based on criteria like IQ and recent antibiotic/probiotic use.
Results
Children with ASD showed lower fecal levels of specific tryptophan-related metabolites, including kynurenate. These lower levels were associated with altered activity in insular and cingulate cortices, brain regions relevant to ASD. Brain activity in the mid-insula and mid-cingulate mediated the relationship between certain gut metabolites (e.g., indolelactate) and ASD symptoms, such as disgust sensitivity. Higher tryptophol levels also correlated with sensory sensitivities in ASD.
Limitations
The study’s cross-sectional design prevents establishing direct cause-and-effect relationships. The strict participant inclusion criteria limited sample size and diversity. Future research requires longitudinal studies or interventional designs to determine causality.
Funding and Disclosures
This research was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD079432) and the Department of Defense’s Idea Development Award (AR170062) [Source: 13.txt]. The authors reported no competing interests.
Publication Information
The paper, “Relationships between brain activity, tryptophan-related gut metabolites, and autism symptomatology,” was published in Nature Communications. It was received on July 12, 2024, accepted on March 24, 2025, and published online on April 14, 2025. Authors include Lisa Aziz-Zadeh, Sofronia M. Ringold, and others [Source: 13.txt]. The DOI is 10.1038/s41467-025-58459-1.